Genetic Variants of FTO Influence Adiposity, Insulin Sensitivity, Leptin Levels, and Resting Metabolic Rate in the Quebec Family Study
Genetic Variants of FTO Influence Adiposity, Insulin Sensitivity, Leptin Levels, and Resting Metabolic Rate in the Quebec Family Study Ron Do 1 , Swneke D. Bailey 1 , Katia Desbiens 2 , Alexandre Belisle 3 , Alexandre Montpetit 3 , Claude Bouchard 4 , Louis Pérusse 5 6 , Marie-Claude Vohl 6 7 and Ja...
Gespeichert in:
| Veröffentlicht in: | Diabetes (New York, N.Y.) N.Y.), 2008-04, Vol.57 (4), p.1147-1150 |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1150 |
|---|---|
| container_issue | 4 |
| container_start_page | 1147 |
| container_title | Diabetes (New York, N.Y.) |
| container_volume | 57 |
| creator | DO, Ron BAILEY, Swneke D DESBIENS, Katia BELISLE, Alexandre MONTPETIT, Alexandre BOUCHARD, Claude PERUSSE, Louis VOHL, Marie-Claude ENGERT, James C |
| description | Genetic Variants of FTO Influence Adiposity, Insulin Sensitivity, Leptin Levels, and Resting Metabolic Rate in the Quebec Family Study
Ron Do 1 ,
Swneke D. Bailey 1 ,
Katia Desbiens 2 ,
Alexandre Belisle 3 ,
Alexandre Montpetit 3 ,
Claude Bouchard 4 ,
Louis Pérusse 5 6 ,
Marie-Claude Vohl 6 7 and
James C. Engert 1 2 6 8
1 Department of Human Genetics, McGill University, Montréal, Québec, Canada
2 Research Institute of the McGill University Health Centre, Montréal, Québec, Canada
3 McGill University and Genome Québec Innovation Centre, Montréal, Québec, Canada
4 Pennington Biomedical Research Center, Baton Rouge, Louisiana
5 Department of Social and Preventive Medicine, Division of Kinesiology, Laval University, Ste-Foy, Québec, Canada
6 Lipid Research Center, Laval University Hospital Research Center, Ste-Foy, Québec, Canada
7 Department of Food Science and Nutrition, Laval University, Ste-Foy, Québec, Canada
8 Department of Medicine, McGill University, Montréal, Québec, Canada
Address correspondence and reprint requests to Dr. James C. Engert, McGill University, Division of Cardiology, Royal Victoria
Hospital, H7.30, 687 Pine Ave. West, Montréal, Québec, Canada H3A 1A1. E-mail: jamie.engert{at}mcgill.ca
Abstract
OBJECTIVE— A genome-wide association study conducted by the Wellcome Trust Case Control Consortium recently associated single nucleotide
polymorphisms (SNPs) in the FTO (fatso/fat mass and obesity associated) gene with type 2 diabetes. These associations were shown to be mediated by obesity.
Other research groups found similar results in Europeans and Hispanics but not African Americans. The mechanism by which FTO influences obesity and type 2 diabetes is currently unknown. The present study investigated the role of two FTO SNPs (rs17817449 and rs1421085) in adiposity, insulin sensitivity, and body weight regulation, including energy intake and
expenditure.
RESEARCH DESIGN AND METHODS— We genotyped 908 individuals from the Quebec City metropolitan area that participated in the Quebec Family Study, a long-term
study of extensively phenotyped individuals designed to investigate factors involved in adiposity.
RESULTS— We found significant associations for both SNPs with several obesity-related phenotypes. In particular, rs17817449 was associated
with BMI ( P = 0.0014 ), weight ( P = 0.0059), and waist circumference ( P = 0.0021) under an additive model. In addition, this FTO SNP influenced fasting insulin ( P = 0.011), homeostasis model assessment of |
| doi_str_mv | 10.2337/db07-1267 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_highw</sourceid><recordid>TN_cdi_highwire_diabetes_diabetes_57_4_1147</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A177721307</galeid><sourcerecordid>A177721307</sourcerecordid><originalsourceid>FETCH-LOGICAL-c654t-30e55c2d43929b55a880fa6edf2911f7bc0da3710605efe7c043bf5d7ef0df7b3</originalsourceid><addsrcrecordid>eNp9kt-KEzEUxgdR3Lp64QtIUBTEnTV_ZiYzl6XYulAp7q7iXcgkJ22WNFMnmdW-gM9taovLSpFzkfDldz5ODl-WPSf4nDLG3-sW85zQij_IRqRhTc4o__YwG2FMaE54w0-yJyHcYIyrVI-zE1IzUrGyHmW_ZuAhWoW-yt5KHwPqDJpeL9CFN24ArwCNtd10wcbtWRLD4KxHV-CTYG__iHPYxKTN4RZcOEPSa3QJIUlL9AmibDuX7C9lBJSouAL0eYAWFJrKtXVbdBUHvX2aPTLSBXh2OE-zL9MP15OP-Xwxu5iM57mqyiLmDENZKqoL1tCmLUtZ19jICrShDSGGtwpryThJvyzBAFe4YK0pNQeDdXpmp9mbve-m774PaUqxtkGBc9JDNwTBcVFSQnkCX_4D3nRD79NsgpKqqAte0QS92kNL6UBYb7rYS7VzFGPCOaeE4Z1VfoRapr330nUejE3yPf78CJ9Kw9qqow1v7zUkJsLPuJRDCKKezf83zIFVnXOwBJGWPVkc9VZ9F0IPRmx6u5b9VhAsduETu_CJXfgS--Kws6Fdg74jD2lLwOsDIIOSzvTSKxv-chRTWhNaJO7dnlvZ5eqH7UFoK1uIEO4uJReFIKTg7DdI_-w3</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>216484762</pqid></control><display><type>article</type><title>Genetic Variants of FTO Influence Adiposity, Insulin Sensitivity, Leptin Levels, and Resting Metabolic Rate in the Quebec Family Study</title><source>MEDLINE</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><creator>DO, Ron ; BAILEY, Swneke D ; DESBIENS, Katia ; BELISLE, Alexandre ; MONTPETIT, Alexandre ; BOUCHARD, Claude ; PERUSSE, Louis ; VOHL, Marie-Claude ; ENGERT, James C</creator><creatorcontrib>DO, Ron ; BAILEY, Swneke D ; DESBIENS, Katia ; BELISLE, Alexandre ; MONTPETIT, Alexandre ; BOUCHARD, Claude ; PERUSSE, Louis ; VOHL, Marie-Claude ; ENGERT, James C</creatorcontrib><description>Genetic Variants of FTO Influence Adiposity, Insulin Sensitivity, Leptin Levels, and Resting Metabolic Rate in the Quebec Family Study
Ron Do 1 ,
Swneke D. Bailey 1 ,
Katia Desbiens 2 ,
Alexandre Belisle 3 ,
Alexandre Montpetit 3 ,
Claude Bouchard 4 ,
Louis Pérusse 5 6 ,
Marie-Claude Vohl 6 7 and
James C. Engert 1 2 6 8
1 Department of Human Genetics, McGill University, Montréal, Québec, Canada
2 Research Institute of the McGill University Health Centre, Montréal, Québec, Canada
3 McGill University and Genome Québec Innovation Centre, Montréal, Québec, Canada
4 Pennington Biomedical Research Center, Baton Rouge, Louisiana
5 Department of Social and Preventive Medicine, Division of Kinesiology, Laval University, Ste-Foy, Québec, Canada
6 Lipid Research Center, Laval University Hospital Research Center, Ste-Foy, Québec, Canada
7 Department of Food Science and Nutrition, Laval University, Ste-Foy, Québec, Canada
8 Department of Medicine, McGill University, Montréal, Québec, Canada
Address correspondence and reprint requests to Dr. James C. Engert, McGill University, Division of Cardiology, Royal Victoria
Hospital, H7.30, 687 Pine Ave. West, Montréal, Québec, Canada H3A 1A1. E-mail: jamie.engert{at}mcgill.ca
Abstract
OBJECTIVE— A genome-wide association study conducted by the Wellcome Trust Case Control Consortium recently associated single nucleotide
polymorphisms (SNPs) in the FTO (fatso/fat mass and obesity associated) gene with type 2 diabetes. These associations were shown to be mediated by obesity.
Other research groups found similar results in Europeans and Hispanics but not African Americans. The mechanism by which FTO influences obesity and type 2 diabetes is currently unknown. The present study investigated the role of two FTO SNPs (rs17817449 and rs1421085) in adiposity, insulin sensitivity, and body weight regulation, including energy intake and
expenditure.
RESEARCH DESIGN AND METHODS— We genotyped 908 individuals from the Quebec City metropolitan area that participated in the Quebec Family Study, a long-term
study of extensively phenotyped individuals designed to investigate factors involved in adiposity.
RESULTS— We found significant associations for both SNPs with several obesity-related phenotypes. In particular, rs17817449 was associated
with BMI ( P = 0.0014 ), weight ( P = 0.0059), and waist circumference ( P = 0.0021) under an additive model. In addition, this FTO SNP influenced fasting insulin ( P = 0.011), homeostasis model assessment of insulin resistance ( P = 0.038), and an insulin sensitivity index derived from an oral glucose tolerance test ( P = 0.0091). Associations were also found with resting metabolic rate (RMR) ( P = 0.042) and plasma leptin levels ( P = 0.036). Adjustment for BMI abolished the associations with insulin sensitivity, RMR, and plasma leptin levels.
CONCLUSIONS— These results confirm that genetic variation at the FTO locus contributes to the etiology of obesity, insulin resistance, and increased plasma leptin levels.
FFM, fat-free mass
FM, fat mass
HOMA-IR, homeostasis model assessment of insulin resistance
HWE, Hardy-Weinberg equilibrium
ISI, insulin sensitivity index
LD, linkage disequilibrium
MAF, minor allele frequency
MCR, metabolic clearance rate
OGTT, oral glucose tolerance test
QFS, Quebec Family Study
RFLP, restriction fragment–length polymorphism
RMR, resting metabolic rate
SNP, single nucleotide polymorphism
Footnotes
Published ahead of print at http://diabetes.diabetesjournals.org on 3 March 2008. DOI: 10.2337/db07-1267.
Additional information for this article can be found in an online appendix at http://dx.doi.org/10.2337/db07-1267 .
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore
be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Accepted January 14, 2008.
Received September 6, 2007.
DIABETES</description><identifier>ISSN: 0012-1797</identifier><identifier>EISSN: 1939-327X</identifier><identifier>DOI: 10.2337/db07-1267</identifier><identifier>PMID: 18316358</identifier><identifier>CODEN: DIAEAZ</identifier><language>eng</language><publisher>Alexandria, VA: American Diabetes Association</publisher><subject>Adipose tissue ; Adipose tissues ; Adult ; African Americans ; Alpha-Ketoglutarate-Dependent Dioxygenase FTO ; Biological and medical sciences ; Body fat ; Body Mass Index ; Bone Density ; Consortia ; Diabetes ; Diabetes Mellitus, Type 2 - genetics ; Diabetes. Impaired glucose tolerance ; Endocrine pancreas. Apud cells (diseases) ; Endocrinopathies ; Etiopathogenesis. Screening. Investigations. Target tissue resistance ; Family ; Female ; Genetic aspects ; Genetic Variation ; Genomes ; Glucose ; Health aspects ; Homeostasis ; Humans ; Influence ; Insulin ; Insulin resistance ; Leptin - blood ; Male ; Medical sciences ; Metabolism ; Middle Aged ; Obesity ; Obesity - genetics ; Polymorphism ; Polymorphism, Single Nucleotide ; Proteins - genetics ; Quebec ; Research design ; Type 2 diabetes</subject><ispartof>Diabetes (New York, N.Y.), 2008-04, Vol.57 (4), p.1147-1150</ispartof><rights>2008 INIST-CNRS</rights><rights>COPYRIGHT 2008 American Diabetes Association</rights><rights>Copyright American Diabetes Association Apr 2008</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c654t-30e55c2d43929b55a880fa6edf2911f7bc0da3710605efe7c043bf5d7ef0df7b3</citedby><cites>FETCH-LOGICAL-c654t-30e55c2d43929b55a880fa6edf2911f7bc0da3710605efe7c043bf5d7ef0df7b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27923,27924</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20228124$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18316358$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>DO, Ron</creatorcontrib><creatorcontrib>BAILEY, Swneke D</creatorcontrib><creatorcontrib>DESBIENS, Katia</creatorcontrib><creatorcontrib>BELISLE, Alexandre</creatorcontrib><creatorcontrib>MONTPETIT, Alexandre</creatorcontrib><creatorcontrib>BOUCHARD, Claude</creatorcontrib><creatorcontrib>PERUSSE, Louis</creatorcontrib><creatorcontrib>VOHL, Marie-Claude</creatorcontrib><creatorcontrib>ENGERT, James C</creatorcontrib><title>Genetic Variants of FTO Influence Adiposity, Insulin Sensitivity, Leptin Levels, and Resting Metabolic Rate in the Quebec Family Study</title><title>Diabetes (New York, N.Y.)</title><addtitle>Diabetes</addtitle><description>Genetic Variants of FTO Influence Adiposity, Insulin Sensitivity, Leptin Levels, and Resting Metabolic Rate in the Quebec Family Study
Ron Do 1 ,
Swneke D. Bailey 1 ,
Katia Desbiens 2 ,
Alexandre Belisle 3 ,
Alexandre Montpetit 3 ,
Claude Bouchard 4 ,
Louis Pérusse 5 6 ,
Marie-Claude Vohl 6 7 and
James C. Engert 1 2 6 8
1 Department of Human Genetics, McGill University, Montréal, Québec, Canada
2 Research Institute of the McGill University Health Centre, Montréal, Québec, Canada
3 McGill University and Genome Québec Innovation Centre, Montréal, Québec, Canada
4 Pennington Biomedical Research Center, Baton Rouge, Louisiana
5 Department of Social and Preventive Medicine, Division of Kinesiology, Laval University, Ste-Foy, Québec, Canada
6 Lipid Research Center, Laval University Hospital Research Center, Ste-Foy, Québec, Canada
7 Department of Food Science and Nutrition, Laval University, Ste-Foy, Québec, Canada
8 Department of Medicine, McGill University, Montréal, Québec, Canada
Address correspondence and reprint requests to Dr. James C. Engert, McGill University, Division of Cardiology, Royal Victoria
Hospital, H7.30, 687 Pine Ave. West, Montréal, Québec, Canada H3A 1A1. E-mail: jamie.engert{at}mcgill.ca
Abstract
OBJECTIVE— A genome-wide association study conducted by the Wellcome Trust Case Control Consortium recently associated single nucleotide
polymorphisms (SNPs) in the FTO (fatso/fat mass and obesity associated) gene with type 2 diabetes. These associations were shown to be mediated by obesity.
Other research groups found similar results in Europeans and Hispanics but not African Americans. The mechanism by which FTO influences obesity and type 2 diabetes is currently unknown. The present study investigated the role of two FTO SNPs (rs17817449 and rs1421085) in adiposity, insulin sensitivity, and body weight regulation, including energy intake and
expenditure.
RESEARCH DESIGN AND METHODS— We genotyped 908 individuals from the Quebec City metropolitan area that participated in the Quebec Family Study, a long-term
study of extensively phenotyped individuals designed to investigate factors involved in adiposity.
RESULTS— We found significant associations for both SNPs with several obesity-related phenotypes. In particular, rs17817449 was associated
with BMI ( P = 0.0014 ), weight ( P = 0.0059), and waist circumference ( P = 0.0021) under an additive model. In addition, this FTO SNP influenced fasting insulin ( P = 0.011), homeostasis model assessment of insulin resistance ( P = 0.038), and an insulin sensitivity index derived from an oral glucose tolerance test ( P = 0.0091). Associations were also found with resting metabolic rate (RMR) ( P = 0.042) and plasma leptin levels ( P = 0.036). Adjustment for BMI abolished the associations with insulin sensitivity, RMR, and plasma leptin levels.
CONCLUSIONS— These results confirm that genetic variation at the FTO locus contributes to the etiology of obesity, insulin resistance, and increased plasma leptin levels.
FFM, fat-free mass
FM, fat mass
HOMA-IR, homeostasis model assessment of insulin resistance
HWE, Hardy-Weinberg equilibrium
ISI, insulin sensitivity index
LD, linkage disequilibrium
MAF, minor allele frequency
MCR, metabolic clearance rate
OGTT, oral glucose tolerance test
QFS, Quebec Family Study
RFLP, restriction fragment–length polymorphism
RMR, resting metabolic rate
SNP, single nucleotide polymorphism
Footnotes
Published ahead of print at http://diabetes.diabetesjournals.org on 3 March 2008. DOI: 10.2337/db07-1267.
Additional information for this article can be found in an online appendix at http://dx.doi.org/10.2337/db07-1267 .
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore
be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Accepted January 14, 2008.
Received September 6, 2007.
DIABETES</description><subject>Adipose tissue</subject><subject>Adipose tissues</subject><subject>Adult</subject><subject>African Americans</subject><subject>Alpha-Ketoglutarate-Dependent Dioxygenase FTO</subject><subject>Biological and medical sciences</subject><subject>Body fat</subject><subject>Body Mass Index</subject><subject>Bone Density</subject><subject>Consortia</subject><subject>Diabetes</subject><subject>Diabetes Mellitus, Type 2 - genetics</subject><subject>Diabetes. Impaired glucose tolerance</subject><subject>Endocrine pancreas. Apud cells (diseases)</subject><subject>Endocrinopathies</subject><subject>Etiopathogenesis. Screening. Investigations. Target tissue resistance</subject><subject>Family</subject><subject>Female</subject><subject>Genetic aspects</subject><subject>Genetic Variation</subject><subject>Genomes</subject><subject>Glucose</subject><subject>Health aspects</subject><subject>Homeostasis</subject><subject>Humans</subject><subject>Influence</subject><subject>Insulin</subject><subject>Insulin resistance</subject><subject>Leptin - blood</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Metabolism</subject><subject>Middle Aged</subject><subject>Obesity</subject><subject>Obesity - genetics</subject><subject>Polymorphism</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Proteins - genetics</subject><subject>Quebec</subject><subject>Research design</subject><subject>Type 2 diabetes</subject><issn>0012-1797</issn><issn>1939-327X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp9kt-KEzEUxgdR3Lp64QtIUBTEnTV_ZiYzl6XYulAp7q7iXcgkJ22WNFMnmdW-gM9taovLSpFzkfDldz5ODl-WPSf4nDLG3-sW85zQij_IRqRhTc4o__YwG2FMaE54w0-yJyHcYIyrVI-zE1IzUrGyHmW_ZuAhWoW-yt5KHwPqDJpeL9CFN24ArwCNtd10wcbtWRLD4KxHV-CTYG__iHPYxKTN4RZcOEPSa3QJIUlL9AmibDuX7C9lBJSouAL0eYAWFJrKtXVbdBUHvX2aPTLSBXh2OE-zL9MP15OP-Xwxu5iM57mqyiLmDENZKqoL1tCmLUtZ19jICrShDSGGtwpryThJvyzBAFe4YK0pNQeDdXpmp9mbve-m774PaUqxtkGBc9JDNwTBcVFSQnkCX_4D3nRD79NsgpKqqAte0QS92kNL6UBYb7rYS7VzFGPCOaeE4Z1VfoRapr330nUejE3yPf78CJ9Kw9qqow1v7zUkJsLPuJRDCKKezf83zIFVnXOwBJGWPVkc9VZ9F0IPRmx6u5b9VhAsduETu_CJXfgS--Kws6Fdg74jD2lLwOsDIIOSzvTSKxv-chRTWhNaJO7dnlvZ5eqH7UFoK1uIEO4uJReFIKTg7DdI_-w3</recordid><startdate>20080401</startdate><enddate>20080401</enddate><creator>DO, Ron</creator><creator>BAILEY, Swneke D</creator><creator>DESBIENS, Katia</creator><creator>BELISLE, Alexandre</creator><creator>MONTPETIT, Alexandre</creator><creator>BOUCHARD, Claude</creator><creator>PERUSSE, Louis</creator><creator>VOHL, Marie-Claude</creator><creator>ENGERT, James C</creator><general>American Diabetes Association</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>8GL</scope><scope>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8AF</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BEC</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>HCIFZ</scope><scope>K9-</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M2P</scope><scope>M7P</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>S0X</scope><scope>7X8</scope></search><sort><creationdate>20080401</creationdate><title>Genetic Variants of FTO Influence Adiposity, Insulin Sensitivity, Leptin Levels, and Resting Metabolic Rate in the Quebec Family Study</title><author>DO, Ron ; BAILEY, Swneke D ; DESBIENS, Katia ; BELISLE, Alexandre ; MONTPETIT, Alexandre ; BOUCHARD, Claude ; PERUSSE, Louis ; VOHL, Marie-Claude ; ENGERT, James C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c654t-30e55c2d43929b55a880fa6edf2911f7bc0da3710605efe7c043bf5d7ef0df7b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Adipose tissue</topic><topic>Adipose tissues</topic><topic>Adult</topic><topic>African Americans</topic><topic>Alpha-Ketoglutarate-Dependent Dioxygenase FTO</topic><topic>Biological and medical sciences</topic><topic>Body fat</topic><topic>Body Mass Index</topic><topic>Bone Density</topic><topic>Consortia</topic><topic>Diabetes</topic><topic>Diabetes Mellitus, Type 2 - genetics</topic><topic>Diabetes. Impaired glucose tolerance</topic><topic>Endocrine pancreas. Apud cells (diseases)</topic><topic>Endocrinopathies</topic><topic>Etiopathogenesis. Screening. Investigations. Target tissue resistance</topic><topic>Family</topic><topic>Female</topic><topic>Genetic aspects</topic><topic>Genetic Variation</topic><topic>Genomes</topic><topic>Glucose</topic><topic>Health aspects</topic><topic>Homeostasis</topic><topic>Humans</topic><topic>Influence</topic><topic>Insulin</topic><topic>Insulin resistance</topic><topic>Leptin - blood</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Metabolism</topic><topic>Middle Aged</topic><topic>Obesity</topic><topic>Obesity - genetics</topic><topic>Polymorphism</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Proteins - genetics</topic><topic>Quebec</topic><topic>Research design</topic><topic>Type 2 diabetes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>DO, Ron</creatorcontrib><creatorcontrib>BAILEY, Swneke D</creatorcontrib><creatorcontrib>DESBIENS, Katia</creatorcontrib><creatorcontrib>BELISLE, Alexandre</creatorcontrib><creatorcontrib>MONTPETIT, Alexandre</creatorcontrib><creatorcontrib>BOUCHARD, Claude</creatorcontrib><creatorcontrib>PERUSSE, Louis</creatorcontrib><creatorcontrib>VOHL, Marie-Claude</creatorcontrib><creatorcontrib>ENGERT, James C</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: High School</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>eLibrary</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>SciTech Premium Collection</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>SIRS Editorial</collection><collection>MEDLINE - Academic</collection><jtitle>Diabetes (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>DO, Ron</au><au>BAILEY, Swneke D</au><au>DESBIENS, Katia</au><au>BELISLE, Alexandre</au><au>MONTPETIT, Alexandre</au><au>BOUCHARD, Claude</au><au>PERUSSE, Louis</au><au>VOHL, Marie-Claude</au><au>ENGERT, James C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genetic Variants of FTO Influence Adiposity, Insulin Sensitivity, Leptin Levels, and Resting Metabolic Rate in the Quebec Family Study</atitle><jtitle>Diabetes (New York, N.Y.)</jtitle><addtitle>Diabetes</addtitle><date>2008-04-01</date><risdate>2008</risdate><volume>57</volume><issue>4</issue><spage>1147</spage><epage>1150</epage><pages>1147-1150</pages><issn>0012-1797</issn><eissn>1939-327X</eissn><coden>DIAEAZ</coden><abstract>Genetic Variants of FTO Influence Adiposity, Insulin Sensitivity, Leptin Levels, and Resting Metabolic Rate in the Quebec Family Study
Ron Do 1 ,
Swneke D. Bailey 1 ,
Katia Desbiens 2 ,
Alexandre Belisle 3 ,
Alexandre Montpetit 3 ,
Claude Bouchard 4 ,
Louis Pérusse 5 6 ,
Marie-Claude Vohl 6 7 and
James C. Engert 1 2 6 8
1 Department of Human Genetics, McGill University, Montréal, Québec, Canada
2 Research Institute of the McGill University Health Centre, Montréal, Québec, Canada
3 McGill University and Genome Québec Innovation Centre, Montréal, Québec, Canada
4 Pennington Biomedical Research Center, Baton Rouge, Louisiana
5 Department of Social and Preventive Medicine, Division of Kinesiology, Laval University, Ste-Foy, Québec, Canada
6 Lipid Research Center, Laval University Hospital Research Center, Ste-Foy, Québec, Canada
7 Department of Food Science and Nutrition, Laval University, Ste-Foy, Québec, Canada
8 Department of Medicine, McGill University, Montréal, Québec, Canada
Address correspondence and reprint requests to Dr. James C. Engert, McGill University, Division of Cardiology, Royal Victoria
Hospital, H7.30, 687 Pine Ave. West, Montréal, Québec, Canada H3A 1A1. E-mail: jamie.engert{at}mcgill.ca
Abstract
OBJECTIVE— A genome-wide association study conducted by the Wellcome Trust Case Control Consortium recently associated single nucleotide
polymorphisms (SNPs) in the FTO (fatso/fat mass and obesity associated) gene with type 2 diabetes. These associations were shown to be mediated by obesity.
Other research groups found similar results in Europeans and Hispanics but not African Americans. The mechanism by which FTO influences obesity and type 2 diabetes is currently unknown. The present study investigated the role of two FTO SNPs (rs17817449 and rs1421085) in adiposity, insulin sensitivity, and body weight regulation, including energy intake and
expenditure.
RESEARCH DESIGN AND METHODS— We genotyped 908 individuals from the Quebec City metropolitan area that participated in the Quebec Family Study, a long-term
study of extensively phenotyped individuals designed to investigate factors involved in adiposity.
RESULTS— We found significant associations for both SNPs with several obesity-related phenotypes. In particular, rs17817449 was associated
with BMI ( P = 0.0014 ), weight ( P = 0.0059), and waist circumference ( P = 0.0021) under an additive model. In addition, this FTO SNP influenced fasting insulin ( P = 0.011), homeostasis model assessment of insulin resistance ( P = 0.038), and an insulin sensitivity index derived from an oral glucose tolerance test ( P = 0.0091). Associations were also found with resting metabolic rate (RMR) ( P = 0.042) and plasma leptin levels ( P = 0.036). Adjustment for BMI abolished the associations with insulin sensitivity, RMR, and plasma leptin levels.
CONCLUSIONS— These results confirm that genetic variation at the FTO locus contributes to the etiology of obesity, insulin resistance, and increased plasma leptin levels.
FFM, fat-free mass
FM, fat mass
HOMA-IR, homeostasis model assessment of insulin resistance
HWE, Hardy-Weinberg equilibrium
ISI, insulin sensitivity index
LD, linkage disequilibrium
MAF, minor allele frequency
MCR, metabolic clearance rate
OGTT, oral glucose tolerance test
QFS, Quebec Family Study
RFLP, restriction fragment–length polymorphism
RMR, resting metabolic rate
SNP, single nucleotide polymorphism
Footnotes
Published ahead of print at http://diabetes.diabetesjournals.org on 3 March 2008. DOI: 10.2337/db07-1267.
Additional information for this article can be found in an online appendix at http://dx.doi.org/10.2337/db07-1267 .
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore
be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Accepted January 14, 2008.
Received September 6, 2007.
DIABETES</abstract><cop>Alexandria, VA</cop><pub>American Diabetes Association</pub><pmid>18316358</pmid><doi>10.2337/db07-1267</doi><tpages>4</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0012-1797 |
| ispartof | Diabetes (New York, N.Y.), 2008-04, Vol.57 (4), p.1147-1150 |
| issn | 0012-1797 1939-327X |
| language | eng |
| recordid | cdi_highwire_diabetes_diabetes_57_4_1147 |
| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Adipose tissue Adipose tissues Adult African Americans Alpha-Ketoglutarate-Dependent Dioxygenase FTO Biological and medical sciences Body fat Body Mass Index Bone Density Consortia Diabetes Diabetes Mellitus, Type 2 - genetics Diabetes. Impaired glucose tolerance Endocrine pancreas. Apud cells (diseases) Endocrinopathies Etiopathogenesis. Screening. Investigations. Target tissue resistance Family Female Genetic aspects Genetic Variation Genomes Glucose Health aspects Homeostasis Humans Influence Insulin Insulin resistance Leptin - blood Male Medical sciences Metabolism Middle Aged Obesity Obesity - genetics Polymorphism Polymorphism, Single Nucleotide Proteins - genetics Quebec Research design Type 2 diabetes |
| title | Genetic Variants of FTO Influence Adiposity, Insulin Sensitivity, Leptin Levels, and Resting Metabolic Rate in the Quebec Family Study |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-12T11%3A50%3A01IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_highw&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Genetic%20Variants%20of%20FTO%20Influence%20Adiposity,%20Insulin%20Sensitivity,%20Leptin%20Levels,%20and%20Resting%20Metabolic%20Rate%20in%20the%20Quebec%20Family%20Study&rft.jtitle=Diabetes%20(New%20York,%20N.Y.)&rft.au=DO,%20Ron&rft.date=2008-04-01&rft.volume=57&rft.issue=4&rft.spage=1147&rft.epage=1150&rft.pages=1147-1150&rft.issn=0012-1797&rft.eissn=1939-327X&rft.coden=DIAEAZ&rft_id=info:doi/10.2337/db07-1267&rft_dat=%3Cgale_highw%3EA177721307%3C/gale_highw%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=216484762&rft_id=info:pmid/18316358&rft_galeid=A177721307&rfr_iscdi=true |